Microgravity-Induced Fluid Shift and Ophthalmic Changes

Although changes to visual acuity in spaceflight have been observed in some astronauts since the early days of the space program, the impact to the crew was considered minor. Since that time, missions to the International Space Station have extended the typical duration of time spent in microgravity from a few days or weeks to many months. This has been accompanied by the emergence of a variety of ophthalmic pathologies in a significant proportion of long-duration crewmembers, including globe flattening, choroidal folding, optic disc edema, and optic nerve kinking, among others. The clinical findings of affected astronauts are reminiscent of terrestrial pathologies such as idiopathic intracranial hypertension that are characterized by high intracranial pressure. As a result, NASA has placed an emphasis on determining the relevant factors and their interactions that are responsible for detrimental ophthalmic response to space. This article will describe the Visual Impairment and Intracranial Pressure syndrome, link it to key factors in physiological adaptation to the microgravity environment, particularly a cephalad shifting of bodily fluids, and discuss the implications for ocular biomechanics and physiological function in long-duration spaceflight.

[1]  Li Li,et al.  Intraocular pressure and ocular perfusion pressure in myopes during 21 min head-down rest. , 2010, Aviation, space, and environmental medicine.

[2]  Mette S. Olufsen,et al.  Modeling cerebral blood flow and regulation , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[3]  Y. Kawai,et al.  Effects of Microgravity on Cerebral Hemodynamics , 2003 .

[4]  V. Nangia,et al.  Intraocular pressure and associated factors: the central India eye and medical study , 2010, Journal of glaucoma.

[5]  J. Haan,et al.  Space Headache: A New Secondary Headache , 2009, Cephalalgia : an international journal of headache.

[6]  G. W. Hoffler,et al.  Apollo space crew cardiovascular evaluations. , 1974, Aerospace medicine.

[7]  T. Mader,et al.  Intraocular pressure and retinal vascular changes during transient exposure to microgravity. , 1993, American journal of ophthalmology.

[8]  A. Aubert,et al.  Adaptation of the Main Peripheral Artery and Vein to Long Term Confinement (MARS 500) , 2014, PloS one.

[9]  R. Black,et al.  Modelling the lymphatic system: challenges and opportunities , 2012, Journal of The Royal Society Interface.

[10]  Daniel J. R. Christensen,et al.  Sleep Drives Metabolite Clearance from the Adult Brain , 2013, Science.

[11]  M. Johnston,et al.  Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species , 2004, Cerebrospinal Fluid Research.

[12]  C. Gans,et al.  Biomechanics: Motion, Flow, Stress, and Growth , 1990 .

[13]  B. Godley,et al.  The effect of microgravity on ocular structures and visual function: a review. , 2013, Survey of ophthalmology.

[14]  L. E. Warren,et al.  Long-duration head-down bed rest: project overview, vital signs, and fluid balance. , 2009, Aviation, space, and environmental medicine.

[15]  C S Leach Fluid control mechanisms in weightlessness. , 1987, Aviation, space, and environmental medicine.

[16]  A. Klawonn,et al.  On the mechanical modeling of anisotropic biological soft tissue and iterative parallel solution strategies , 2010 .

[17]  M. Kahn Color Doppler Orbital Hemodynamics in Healthy Individuals and Patients with Vascular Disorders in Taiwan , 2008, Orbit.

[18]  C. Alessandri,et al.  Functional changes cardiovascular: normobaric activity and microgravity in young healthy human subjects. , 2012, European review for medical and pharmacological sciences.

[19]  Brian J. Motil,et al.  Microgravity Fluids and Combustion Research at NASA Glenn Research Center , 2013 .

[20]  C. Delaey,et al.  Regulatory Mechanisms in the Retinal and Choroidal Circulation , 2000, Ophthalmic Research.

[21]  D. Menon,et al.  Use of T2-weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure , 2008, Critical care.

[22]  A. Aubert,et al.  Spectral characteristics of heart rate fluctuations during parabolic flight , 2005, European Journal of Applied Physiology.

[23]  Rong Zhang,et al.  Human cerebral autoregulation before, during and after spaceflight , 2007, The Journal of physiology.

[24]  R. Klingebiel,et al.  Structural Olfactory Nerve Changes in Patients Suffering from Idiopathic Intracranial Hypertension , 2012, PloS one.

[25]  G T Feke,et al.  Blood flow in the normal human retina. , 1989, Investigative ophthalmology & visual science.

[26]  P. Mitchell,et al.  Intraocular pressure over the clinical range of blood pressure: blue mountains eye study findings. , 2005, American journal of ophthalmology.

[27]  A. Sit,et al.  Effect of head and body position on intraocular pressure. , 2012, Ophthalmology.

[28]  Josh Wallman,et al.  The multifunctional choroid , 2010, Progress in Retinal and Eye Research.

[29]  Yoshiki Sugiyama,et al.  Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre , 2002, The Journal of physiology.

[30]  S. Smith,et al.  Nutritional biochemistry of space flight. , 2009, Life support & biosphere science : international journal of earth space.

[31]  J.M.A. Lenihan,et al.  Biomechanics — Mechanical properties of living tissue , 1982 .

[32]  M. Ursino,et al.  A simple mathematical model of the interaction between intracranial pressure and cerebral hemodynamics. , 1997, Journal of applied physiology.

[33]  Yubing Shi,et al.  Review of Zero-D and 1-D Models of Blood Flow in the Cardiovascular System , 2011, Biomedical engineering online.

[34]  Robert A Pietrzyk,et al.  Renal stone formation among astronauts. , 2007, Aviation, space, and environmental medicine.

[35]  Andreas A. Linninger,et al.  Normal and Hydrocephalic Brain Dynamics: The Role of Reduced Cerebrospinal Fluid Reabsorption in Ventricular Enlargement , 2009, Annals of Biomedical Engineering.

[36]  C S Leach,et al.  Influence of spaceflight on erythrokinetics in man. , 1984, Science.

[37]  V. Convertino,et al.  Back pain during 6 degrees head-down tilt approximates that during actual microgravity. , 1995, Aviation, space, and environmental medicine.

[38]  D. Benhamou,et al.  Ocular sonography in patients with raised intracranial pressure: the papilloedema revisited , 2008, Critical care.

[39]  Stephan J. Schreiber,et al.  How does the blood leave the brain? A systematic ultrasound analysis of cerebral venous drainage patterns , 2004, Neuroradiology.

[40]  L. Schmetterer,et al.  Retinal blood flow in healthy young subjects. , 2012, Investigative ophthalmology & visual science.

[41]  J. Brady,et al.  Crewmember performance before, during, and after spaceflight. , 2005, Journal of the experimental analysis of behavior.

[42]  Copyrighted Mat rial-Taylor Space physiology and medicine , 2016 .

[43]  Pierre Denise,et al.  Effect of human head flexion on the control of peripheral blood flow in microgravity and in 1 g , 2002, European Journal of Applied Physiology.

[44]  Atsuo Tomidokoro,et al.  In vivo measurement of blood velocity in human major retinal vessels using the laser speckle method. , 2011, Investigative ophthalmology & visual science.

[45]  Khader M Hasan,et al.  Orbital and intracranial effects of microgravity: findings at 3-T MR imaging. , 2012, Radiology.

[46]  K. Darge,et al.  Internal jugular venous valves in children: high-resolution US findings , 2001, European Radiology.

[47]  Gilles Clément,et al.  Space physiology II: adaptation of the central nervous system to space flight—past, current, and future studies , 2012, European Journal of Applied Physiology.

[48]  C S Leach,et al.  Regulation of body fluid volume and electrolyte concentrations in spaceflight. , 1997, Advances in space biology and medicine.

[49]  Scott M Smith,et al.  Benefits for bone from resistance exercise and nutrition in long‐duration spaceflight: Evidence from biochemistry and densitometry , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[50]  W E Thornton,et al.  Space shuttle inflight and postflight fluid shifts measured by leg volume changes. , 1987, Aviation, space, and environmental medicine.

[51]  C. R. Ethier,et al.  Introductory Biomechanics: From Cells to Organisms , 2007 .

[52]  S. Staugaitis,et al.  A technical approach to dissecting and assessing cadaveric veins pertinent to chronic cerebrospinal venous insufficiency in multiple sclerosis , 2012, Neurological research.

[53]  Leopold Schmetterer,et al.  Measurement of absolute blood flow velocity and blood flow in the human retina by dual-beam bidirectional Doppler fourier-domain optical coherence tomography. , 2012, Investigative ophthalmology & visual science.

[54]  Carl E Clarke,et al.  Idiopathic intracranial hypertension , 2006, The Lancet Neurology.

[55]  A P Blaber,et al.  Impaired cerebrovascular autoregulation and reduced CO₂ reactivity after long duration spaceflight. , 2012, American journal of physiology. Heart and circulatory physiology.

[56]  A Guell,et al.  Cardiovascular and hormonal response during a 4-week head-down tilt with and without exercise and LBNP countermeasures. , 1996, Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology.

[57]  Yongkang Chen,et al.  The capillary flow experiments aboard the International Space Station: Status , 2009 .

[58]  G. E. Vates,et al.  A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β , 2012, Science Translational Medicine.

[59]  T. Driscoll,et al.  Control of red blood cell mass in spaceflight. , 1996, Journal of applied physiology.

[60]  S. Shea,et al.  Adverse Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption , 2012, Science Translational Medicine.

[61]  Y. Fung,et al.  Biomechanics: Mechanical Properties of Living Tissues , 1981 .

[62]  R. Nolan,et al.  Dynamic responsiveness of the vascular bed as a regulatory mechanism in vasomotor control , 2009, The Journal of general physiology.

[63]  Y. Fung Mechanical Properties and Active Remodeling of Blood Vessels , 1993 .

[64]  Paolo Galluzzi,et al.  Quantitative ColourDopplerSonography Evaluation of Cerebral Venous Outflow: A Comparative Study between Patients with Multiple Sclerosis and Controls , 2011, PloS one.

[65]  H. Gunga,et al.  Anemia and erythropoietin in space flights. , 2005, Seminars in nephrology.

[66]  A R Hargens,et al.  Recent bed rest results and countermeasure development at NASA. , 1994, Acta physiologica Scandinavica. Supplementum.

[67]  L. Carichino,et al.  Cerebrospinal fluid pressure and glaucoma: regulation of trans-lamina cribrosa pressure , 2013, British Journal of Ophthalmology.

[68]  Noam Alperin,et al.  Noninvasive Intracranial Compliance From MRI-Based Measurements of Transcranial Blood and CSF Flows: Indirect Versus Direct Approach , 2009, IEEE Transactions on Biomedical Engineering.

[69]  R. Ritch,et al.  Posture-induced intraocular pressure changes: considerations regarding body position in glaucoma patients. , 2010, Survey of ophthalmology.

[70]  B. Yalcin,et al.  Vortex veins: Anatomic investigations on human eyes , 2005, Clinical anatomy.

[71]  Dao-Yi Yu,et al.  The translaminar pressure gradient in sustained zero gravity, idiopathic intracranial hypertension, and glaucoma. , 2012, Medical hypotheses.

[72]  L. Schmetterer,et al.  Ocular hemodynamics during isometric exercise. , 2001, Microvascular research.

[73]  J. Flammer,et al.  Autoregulation, a balancing act between supply and demand. , 2008, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[74]  J. McLaren,et al.  Effect of body position on intraocular pressure and aqueous flow. , 1987, Investigative ophthalmology & visual science.

[75]  M. W. Bungo,et al.  Acute Hemodynamic Responses to Weightlessness in Humans , 1989, Journal of clinical pharmacology.

[76]  D. Hill,et al.  Retinal vessel responses to passive tilting , 1990, Eye.

[77]  N. Goswami,et al.  Cerebrovascular autoregulation: lessons learned from spaceflight research , 2012, European Journal of Applied Physiology.

[78]  C Drummer,et al.  Validity of microgravity simulation models on earth. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[79]  C. Chiquet,et al.  Changes in Intraocular Pressure during Prolonged (7-Day) Head-Down Tilt Bedrest , 2003, Journal of glaucoma.

[80]  Chun-Yu Cheng,et al.  Internal jugular venous abnormalities in transient monocular blindness , 2013, BMC Neurology.

[81]  Wayne W. Wakeland,et al.  A review of physiological simulation models of intracranial pressure dynamics , 2008, Comput. Biol. Medicine.

[82]  J. Arciero,et al.  Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents. , 2013, Journal of coupled systems and multiscale dynamics.

[83]  Irina Alferova,et al.  Adaptation of the left heart, cerebral and femoral arteries, and jugular and femoral veins during short- and long-term head-down tilt and spaceflights , 2001, European Journal of Applied Physiology.

[84]  H. Hinghofer-Szalkay Gravity, the hydrostatic indifference concept and the cardiovascular system , 2011, European Journal of Applied Physiology.

[85]  Mohammad Kassemi,et al.  Impact of weightlessness on cardiac shape and left ventricular stress/strain distributions. , 2013, Journal of biomechanical engineering.

[86]  J. Jonas,et al.  Body Height, Estimated Cerebrospinal Fluid Pressure and Open-Angle Glaucoma. The Beijing Eye Study 2011 , 2014, PloS one.

[87]  W. Edwards,et al.  Venous valves in subclavian and internal jugular veins. Frequency, position, and structure in 100 autopsy cases. , 1987, The American journal of cardiovascular pathology.

[88]  S. Rajulu,et al.  The Effects of Microgravity on Seated Height (Spinal Elongation) , 2011 .

[89]  J M Seelig,et al.  Comparative responses of cerebellar and cerebral arterioles to changes in PaCO2 in cats. , 1984, The American journal of physiology.

[90]  J. Jonas Trans-lamina cribrosa pressure difference. , 2007, Archives of ophthalmology.

[91]  V. Convertino Clinical aspects of the control of plasma volume at microgravity and during return to one gravity. , 1996, Medicine and science in sports and exercise.

[92]  J. Bullock,et al.  The origin of choroidal folds a clinical, histopathological, and experimental study , 1974, Documenta Ophthalmologica.

[93]  Sarah L Hosking,et al.  Non-invasive vascular impedance measures demonstrate ocular vasoconstriction during isometric exercise , 2006, British Journal of Ophthalmology.

[94]  R. Carare,et al.  Lymphatic drainage of the brain and the pathophysiology of neurological disease , 2008, Acta Neuropathologica.

[95]  Scott A. Stevens,et al.  A whole-body mathematical model for intracranial pressure dynamics , 2003, Journal of mathematical biology.

[96]  S. Hayreh Physiological anatomy of the choroidal vascular bed , 1983, International Ophthalmology.

[97]  A. Sit,et al.  Aqueous humor outflow facility by tonography does not change with body position. , 2010, Investigative ophthalmology & visual science.

[98]  M. Stringer,et al.  Ophthalmic and facial veins are not valveless , 2010, Clinical & experimental ophthalmology.

[99]  Günther Meschke,et al.  Constitutive modeling of crimped collagen fibrils in soft tissues. , 2009, Journal of the mechanical behavior of biomedical materials.

[100]  A. Caprihan,et al.  Effect of head-down tilt on brain water distribution , 1999, European Journal of Applied Physiology and Occupational Physiology.

[101]  R M Lang,et al.  Objective evaluation of changes in left ventricular and atrial volumes during parabolic flight using real-time three-dimensional echocardiography. , 2006, Journal of applied physiology.

[102]  W. Yuh,et al.  MR imaging of pituitary morphology in idiopathic intracranial hypertension , 2000, Journal of magnetic resonance imaging : JMRI.

[103]  P A Low,et al.  Cardiovascular and Valsalva responses during parabolic flight. , 1998, Journal of applied physiology.

[104]  R. Kahn,et al.  Effects of positioning and exercise on intracranial pressure in a neurosurgical intensive care unit. , 1997, Physical therapy.

[105]  C. Mukai,et al.  Acclimation during space flight: effects on human physiology , 2009, Canadian Medical Association Journal.

[106]  G. Kim Prisk,et al.  Invited Review: Microgravity and the lung , 2000 .

[107]  H. Stanley,et al.  Flow in porous media: The , 1984 .

[108]  S. A. Stevens,et al.  Modeling intracranial pressures in microgravity: the influence of the blood-brain barrier. , 2007, Aviation, space, and environmental medicine.

[109]  L F Zhang,et al.  Vascular adaptation to microgravity: what have we learned? , 2001, Journal of applied physiology.

[110]  A R Hargens,et al.  Transcapillary fluid shifts in tissues of the head and neck during and after simulated microgravity. , 1991, Journal of applied physiology.

[111]  A. Degnan,et al.  Pseudotumor Cerebri: Brief Review of Clinical Syndrome and Imaging Findings , 2011, American Journal of Neuroradiology.

[112]  A E Aubert,et al.  Operational point of neural cardiovascular regulation in humans up to 6 months in space. , 2010, Journal of applied physiology.

[113]  Vladimir Pletser,et al.  Short duration microgravity experiments in physical and life sciences during parabolic flights: the first 30 ESA campaigns. , 2004, Acta astronautica.

[114]  J I Leonard,et al.  Regulation of body fluid compartments during short-term spaceflight. , 1996, Journal of applied physiology.

[115]  Francis A. Cucinotta,et al.  How Safe Is Safe Enough? Radiation Risk for a Human Mission to Mars , 2013, PloS one.

[116]  T P Stein,et al.  Nutrition in the space station era , 2001, Nutrition Research Reviews.

[117]  C S Leach-Huntoon,et al.  Decreased production of red blood cells in human subjects exposed to microgravity. , 1995, The Journal of laboratory and clinical medicine.

[118]  S. A. Stevens,et al.  Local Compliance Effects on the Global Pressure-Volume Relationship in Models of Intracranial Pressure Dynamics , 2000 .

[119]  Mark R Campbell,et al.  Risk of herniated nucleus pulposus among U.S. astronauts. , 2010, Aviation, space, and environmental medicine.

[120]  Y. Fung Basic Transport Equations According to Thermodynamics, Molecular Diffusion, Mechanisms in Membranes, and Multiphasic Structure , 1990 .

[121]  U. Rutnin Fundus appearance in normal eyes. I. The choroid. , 1967, American journal of ophthalmology.

[122]  P. Michael Conn,et al.  Sourcebook of models for biomedical research , 2008 .

[123]  J. Humphrey,et al.  A Mixture Model of Arterial Growth and Remodeling in Hypertension: Altered Muscle Tone and Tissue Turnover , 2004, Journal of Vascular Research.

[124]  R. Farrell,et al.  Validity of pulsatile ocular blood flow measurements. , 1994, Survey of ophthalmology.

[125]  T. Stein,et al.  The relationship between dietary intake, exercise, energy balance and the space craft environment , 2000, Pflügers Archiv.

[126]  C. G. Blomqvist,et al.  Central venous pressure and cardiac function during spaceflight. , 1998, Journal of applied physiology.

[127]  Peter Wriggers,et al.  Large strain analysis of soft biological membranes: Formulation and finite element analysis , 1996 .

[128]  S. Brereton Life , 1876, The Indian medical gazette.

[129]  B. Lam,et al.  Evidence for altered spinal canal compliance and cerebral venous drainage in untreated idiopathic intracranial hypertension. , 2012, Acta neurochirurgica. Supplement.

[130]  E. Newman,et al.  Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease , 2012, Progress in Retinal and Eye Research.

[131]  N. Goswami,et al.  Impairment of Cerebral Blood Flow Regulation in Astronauts With Orthostatic Intolerance After Flight , 2011, Stroke.

[132]  Yoel Arieli,et al.  Effect of intraocular pressure on the hemodynamics of the central retinal artery: a mathematical model. , 2014, Mathematical biosciences and engineering : MBE.

[133]  Dao-Yi Yu,et al.  Phenotypic heterogeneity in the endothelium of the human vortex vein system. , 2013, Experimental eye research.

[134]  Y. Fung,et al.  The Meaning of the Constitutive Equation , 1981 .

[135]  P. Gaehtgens,et al.  Flow Properties of the Blood , 1982 .

[136]  Günther Meschke,et al.  A computational remodeling approach to predict the physiological architecture of the collagen fibril network in corneo-scleral shells , 2010, Biomechanics and modeling in mechanobiology.

[137]  D. Silver,et al.  Pressure-volume relation for the living human eye. , 2000, Current eye research.

[138]  D. Schmidt,et al.  The mystery of cotton-wool spots - a review of recent and historical descriptions. , 2008, European journal of medical research.

[139]  N. Eves,et al.  Resistance exercise, the Valsalva maneuver, and cerebrovascular transmural pressure. , 2003, Medicine and science in sports and exercise.

[140]  R. Klingebiel,et al.  Internal jugular vein valve incompetence and intracranial venous anatomy in transient global amnesia , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[141]  Yojiro Ogawa,et al.  Subfoveal choroidal thickness and foveal retinal thickness during head-down tilt. , 2012, Aviation, space, and environmental medicine.

[142]  Minsuok Kim,et al.  A one-dimensional model of the spinal cerebrospinal-fluid compartment. , 2012, Journal of biomechanical engineering.

[143]  Alan R Hargens,et al.  Pathophysiology of low back pain during exposure to microgravity. , 2008, Aviation, space, and environmental medicine.

[144]  D. Friedman,et al.  Distribution of ocular perfusion pressure and its relationship with open-angle glaucoma: the singapore malay eye study. , 2010, Investigative ophthalmology & visual science.

[145]  A. Hargens,et al.  Height increase, neuromuscular function, and back pain during 6 degrees head-down tilt with traction. , 1997, Aviation, space, and environmental medicine.

[146]  Kenol Jules,et al.  Low-gravity Orbiting Research Laboratory Environment Potential Impact on Space Biology Research , 2006 .

[147]  M. Tsilimbaris,et al.  Ocular rigidity, ocular pulse amplitude, and pulsatile ocular blood flow: the effect of intraocular pressure. , 2009, Investigative ophthalmology & visual science.

[148]  W E Thornton,et al.  Changes in leg volume during microgravity simulation. , 1992, Aviation, space, and environmental medicine.

[149]  M. Shiran,et al.  Retinal haemodynamics in individuals with well-controlled type 1 diabetes , 2007, Diabetologia.

[150]  S. Hayreh Posterior ciliary artery circulation in health and disease: the Weisenfeld lecture. , 2004, Investigative ophthalmology & visual science.

[151]  Victor A. Convertino,et al.  Human Models of Space Physiology , 2008 .

[152]  Eric L Kerstman,et al.  Space adaptation back pain: a retrospective study. , 2012, Aviation, space, and environmental medicine.

[153]  J. Wolffsohn,et al.  Aetiology and management of choroidal folds , 1999, Clinical & experimental optometry.

[154]  Emily S. Nelson,et al.  An examination of anticipated g-jitter on Space Station and its effects on materials processes , 1992 .

[155]  A. Linninger,et al.  A Computational Model of Cerebral Vasculature, Brain Tissue, and Cerebrospinal Fluid , 2011 .

[156]  Kwang I. Suh,et al.  Measurement of choroidal blood flow in zero gravity , 2003, SPIE BiOS.

[157]  P. Norsk,et al.  Sympathetic nervous activity decreases during head-down bed rest but not during microgravity. , 2005, Journal of applied physiology.

[158]  J. Kiel,et al.  Choroidal myogenic autoregulation and intraocular pressure. , 1994, Experimental eye research.

[159]  C. McGowan Patients' confidentiality. , 2012, Critical care nurse.

[160]  Karl Kirsch,et al.  Fluid shifts into and out of superficial tissues under microgravity and terrestrial conditions , 1993, The clinical investigator.

[161]  C S Leach,et al.  The endocrine system in space flight. , 1988, Acta astronautica.

[162]  A. Wåhlin,et al.  Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging. , 2013, Investigative ophthalmology & visual science.

[163]  Larry A Kramer,et al.  Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. , 2011, Ophthalmology.

[164]  J. Hunter A mathematical model of idiopathic intracranial hypertension incorporating increased arterial inflow and variable venous outflow collapsibility , 2009 .

[165]  E. Caiani,et al.  The role of echocardiography in the assessment of cardiac function in weightlessness—Our experience during parabolic flights , 2009, Respiratory Physiology & Neurobiology.

[166]  J. Izatt,et al.  Measurement of total blood flow in the normal human retina using Doppler Fourier-domain optical coherence tomography , 2009, British Journal of Ophthalmology.

[167]  D F Doerr,et al.  Restoration of plasma volume after 16 days of head-down tilt induced by a single bout of maximal exercise. , 1996, The American journal of physiology.

[168]  N Foldager,et al.  Central venous pressure in humans during microgravity. , 1996, Journal of applied physiology.

[169]  Daniel L. Feeback,et al.  Muscle volume, MRI relaxation times (T2), and body composition after spaceflight. , 2000, Journal of applied physiology.

[170]  Alan R Hargens,et al.  Intraocular/Intracranial pressure mismatch hypothesis for visual impairment syndrome in space. , 2014, Aviation, space, and environmental medicine.

[171]  T. Mader Intraocular Pressure in Microgravity , 1991, Journal of clinical pharmacology.

[172]  W. Thornton,et al.  Fluid shifts in weightlessness. , 1987, Aviation, space, and environmental medicine.

[173]  R. W. Austin,et al.  Experiment S-8/D-13, visual acuity and astronaut visibility , 1966 .

[174]  William J Dupps,et al.  Biomechanical effects of intraocular pressure elevation on optic nerve/lamina cribrosa before and after peripapillary scleral collagen cross-linking. , 2009, Investigative ophthalmology & visual science.

[175]  Douglas R. Anderson,et al.  Use of colour Doppler imaging in ocular blood flow research , 2011, Acta ophthalmologica.

[176]  Giovanna Guidoboni,et al.  Theoretical analysis of vascular regulatory mechanisms contributing to retinal blood flow autoregulation. , 2013, Investigative ophthalmology & visual science.

[177]  L. Bielory,et al.  The anatomical and functional relationship between allergic conjunctivitis and allergic rhinitis , 2013, Allergy & rhinology.

[178]  A. Lametschwandtner,et al.  Valves in small veins and venules. , 2006, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[179]  R N Weinreb,et al.  Ocular manifestations of gravity inversion. , 1985, JAMA.

[180]  A. Nicolaides,et al.  Screening for chronic cerebrospinal venous insufficiency (CCSVI) using ultrasound: recommendations for a protocol. , 2011, Functional neurology.

[181]  T. Mader,et al.  Intraocular pressure, retinal vascular, and visual acuity changes during 48 hours of 10 degrees head-down tilt. , 1990, Aviation, space, and environmental medicine.

[182]  M. Brodsky,et al.  Magnetic resonance imaging in pseudotumor cerebri. , 1998, Ophthalmology.

[183]  J P Bagian,et al.  Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt. , 1993, Journal of applied physiology.

[184]  B S Bennett,et al.  Acute Hemodynamic Responses to Weightlessness During Parabolic Flight , 1991, Journal of clinical pharmacology.

[185]  Steven H. Platts,et al.  Risk of Orthostatic Intolerance During Re-Exposure to Gravity , 2015 .

[186]  R. W. Fox,et al.  Fox and McDonald's Introduction to Fluid Mechanics , 2011 .

[187]  L Beydon,et al.  Cerebral hemodynamics during arterial and CO(2) pressure changes: in vivo prediction by a mathematical model. , 2000, American journal of physiology. Heart and circulatory physiology.

[188]  Scott A. Stevens,et al.  A Model for Idiopathic Intracranial Hypertension and Associated Pathological ICP Wave-Forms , 2008, IEEE Transactions on Biomedical Engineering.

[189]  C. Riva,et al.  Posture changes and subfoveal choroidal blood flow. , 2004, Investigative ophthalmology & visual science.

[190]  Martina Heer,et al.  Vision changes after spaceflight are related to alterations in folate- and vitamin B-12-dependent one-carbon metabolism. , 2012, The Journal of nutrition.

[191]  Richard L Summers,et al.  Theoretical analysis of the mechanisms of a gender differentiation in the propensity for orthostatic intolerance after spaceflight , 2010, Theoretical Biology and Medical Modelling.

[192]  A LeBlanc,et al.  Bone mineral and lean tissue loss after long duration space flight. , 2000, Journal of musculoskeletal & neuronal interactions.

[193]  J. Karemaker,et al.  Human cerebral venous outflow pathway depends on posture and central venous pressure , 2004, The Journal of physiology.

[194]  R. Gerzer,et al.  Reduced natriuresis during weightlessness , 1993, The clinical investigator.

[195]  A. Gabrielsen,et al.  Vasorelaxation in Space , 2006, Hypertension.

[196]  Martina Heer,et al.  Body fluid regulation in µ-gravity differs from that on Earth: an overview , 2000, Pflügers Archiv.

[197]  A. V. Rij,et al.  Micro‐venous valves in the superficial veins of the human lower limb , 2004, Clinical anatomy.

[198]  D. Selva,et al.  Persistent posterior globe flattening after orbital cavernous haemangioma excision , 2005, Clinical and Experimental Ophthalmology.

[199]  R N Weinreb,et al.  Effect of inverted body position on intraocular pressure. , 1985, American journal of ophthalmology.

[200]  G. W. Hoffler,et al.  Anthropometric changes and fluid shifts , 1977 .

[201]  D. Weissman,et al.  Acute effects of solar particle event radiation , 2014, Journal of Radiation Research.

[202]  M. Ferrari,et al.  Space headache on Earth: Head-down-tilted bed rest studies simulating outer-space microgravity , 2015, Cephalalgia : an international journal of headache.

[203]  C S Leach,et al.  Endocrine responses in long-duration manned space flight. , 1975, Acta astronautica.

[204]  B. Ertl-Wagner,et al.  Determination of cranio‐spinal canal compliance distribution by MRI: Methodology and early application in idiopathic intracranial hypertension , 2011, Journal of magnetic resonance imaging : JMRI.

[205]  Scott A Stevens,et al.  Modeling steady-state intracranial pressures in supine, head-down tilt and microgravity conditions. , 2005, Aviation, space, and environmental medicine.

[206]  High-resolution ultrasound evaluation of internal jugular venous valves , 1999, European Radiology.

[207]  L. Pasquale,et al.  Retinal blood flow response to posture change in glaucoma patients compared with healthy subjects. , 2008, Ophthalmology.